Fig. 4

The tolerogenic and immunostimulatory roles of pDCs in the tumor microenvironment. Graphical illustration of the human pDCs polarization in cancer. pDCs can exert anti-tumor and immunostimulatory functions (left panel), whereas tolerogenic pDCs promote the immune evasion of tumor cells (right panel). Tolerogenic pDCs are depicted as functionally impaired (e.g. I-IFN production) cells by tumor-derived cytokines and oncometabolites. Tolerogenic pDCs are further characterized by expression of costimulatory receptors or coinhibitory molecules and generate an immunosuppressive and inflammatory TME (e.g. Treg expansion). On the contrary, properly activated pDCs (e.g. via TLR7/9 agonists or STING agonists) produce type I and type III IFNs and proinflammatory cytokines (e.g. CXCL10), eliciting the recruitment of adaptive immune cells. Human pDCs can exert direct effector functions against tumor cells, as well. The surface molecules and intracellular mechanisms involved in these functions are detailed. Created with BioRender.com